Affiliation: The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.

ABSTRACT

Background: Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil-lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown.

Methods: This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters.

Results: The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0-1 in 66% and 2-3 in 34%. The median NLR was 3.08 (IQR 2.06-4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P=0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.

Conclusions: NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.

Mentions:
Between July 2004 and February 2014, 4172 patients were considered for phase 1 trial at the Drug Development Unit. Of these, 1308 patients were reviewed for the test cohort, with 300 patients treated in a phase 1 trial (Figure 1). Of these patients, 15% had breast cancer, 13% had colorectal cancer, 13% had ovarian cancer, 13% had non-small cell lung cancer, 14% had prostate cancer and 31% had other tumour types. The performance status was ECOG 0 in 35%, and ECOG 1–2 in 65%. The RMH score was 0–1 in 66% and 2–3 in 34% of patients. The median age was 60 years (interquartile range (IQR) 48–67), and 47% were male. The median absolute neutrophil count was 4.24 × 109 l−1 (IQR 3.06–5.68), and the median absolute lymphocyte count was 1.39 × 109 l−1 (IQR 1.02–1.82). The median NLR was 3.08 (IQR 2.06–4.49; Table 1). Stratification for these parameters for the five main tumour types in the test cohort is summarised in Table 1. The median OS was 8.6 months (95% CI 7.4–10.1), with an event rate of 66% and a median follow-up of 6.9 months.

Mentions:
Between July 2004 and February 2014, 4172 patients were considered for phase 1 trial at the Drug Development Unit. Of these, 1308 patients were reviewed for the test cohort, with 300 patients treated in a phase 1 trial (Figure 1). Of these patients, 15% had breast cancer, 13% had colorectal cancer, 13% had ovarian cancer, 13% had non-small cell lung cancer, 14% had prostate cancer and 31% had other tumour types. The performance status was ECOG 0 in 35%, and ECOG 1–2 in 65%. The RMH score was 0–1 in 66% and 2–3 in 34% of patients. The median age was 60 years (interquartile range (IQR) 48–67), and 47% were male. The median absolute neutrophil count was 4.24 × 109 l−1 (IQR 3.06–5.68), and the median absolute lymphocyte count was 1.39 × 109 l−1 (IQR 1.02–1.82). The median NLR was 3.08 (IQR 2.06–4.49; Table 1). Stratification for these parameters for the five main tumour types in the test cohort is summarised in Table 1. The median OS was 8.6 months (95% CI 7.4–10.1), with an event rate of 66% and a median follow-up of 6.9 months.

Bottom Line:
Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS.In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use.This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.

Affiliation:
The Institute of Cancer Research and the Royal Marsden Hospital, Downs Road, Sutton, Surrey, London SM2 5PT, UK.

ABSTRACT

Background: Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil-lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown.

Methods: This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters.

Results: The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0-1 in 66% and 2-3 in 34%. The median NLR was 3.08 (IQR 2.06-4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P=0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log10NLR models, with an optimal NLR cutoff of 3.0.

Conclusions: NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.